Biological control of weeds is achieved by enhancing the virulence of weed-pathogenic fungi through selection of strains that over-excrete amino acids that cause metabolic disorders in plants. Amino acid synthesis pathways in plants have evolved to economize the metabolic cost of biosynthesis. Misregulation by one amino acid can lead to deficient biosynthesis of two other amino acids in the same pathway. We exploited this metabolic misregulation in several plant pathogens, including our application for Striga hermonthica, the weed causing the most significant crop loss in Africa. We determined that leucine, threonine, and tyrosine each inhibit Striga. Using Fusarium oxysporum fsp. strigae endemic to Kenya, we selected strains for elevated leucine- and tyrosine-excretion to increase the pathogen’s virulence. These strains were embedded on toothpicks and sealed in sterile drinking straws. To grow an on-farm inoculum, farmers incubated the strains in cooked rice for three days, at which point they planted ca 0.5g of the inoculum with each maize seed hill. In 500 paired plots (using hybrid seed and fertilizer) crop yield increased an average of 56% in the long season and 42% in the short season (p < 0.0001, pair-wise t-test). This village-based fresh inoculum is host-specific, inexpensive, safe, effective, and well-received by farmers. We are now assessing the efficacy of virulence-enhanced pathogens for other weeds.